The present outlook for many victims of juvenile onset diabetes mellitus is dismal and successful transplantation of the cadaveric pancreas will make a significant contribution to the suppression or prevention of the frequently disabling or fatal sequelae of diabetes. The limitations to the development of pancreatic transplantation as a routine clinical procedure for treatment of many patients are the hazards of the immunosuppression necessary to suppress rejection and the shortage of organs due to poorly developed and inadequate preservation techniques. The advent of cyclosporin A for immunosuppressive therapy is considered to reduce significantly the hazards of immunosuppression. Thus, this proposal describes methods to solve the second limitation to the clinical adaptation of pancreatic transplantation--the development of reliable preservation of the pancreas for up to 3 days. This objective will be obtained by applying the methods used in our laboratory to study and improve upon kidney preservation. Using a dog model, the effects of hypothermic perfusion on the metabolic integrity of the preserved pancreas will be studied including metabolic parameters related to membrane integrity, intracellular regulation of metabolites and energy metabolism. From this data an appropriate perfusion fluid will be designed to maintain near normal levels of metabolites and metabolic function necessary for organ survival. This will be accomplished by the use of various substrates, cofactors, colloids, electrolytes, and pharmacological agents previously shown to affect the metabolism of preserved organs. The ultimate test of the adequacy of the perfusates designed will be viability and survival in a pancreatic transplant model. Successful preservation obtained in the research laboratory will be applied in our clinical pancreas transplantation program.